The management of recurrent ovarian cancer (OVCA) is a major clinical challenge because relapse after platinum-based front-line chemotherapy currently has no clinical laboratory biomarkers other than CA125 which has limitations. A recent MRC/EORTC trial demonstrated that treatment of OVCA patients with a rising CA125 who received chemotherapy prior to the appearance of clinical symptoms of recurrence had no survival benefit over those for whom therapy was initiated at the time of clinical symptoms of OVCA. New biomarkers of OVCA recurrence are needed to improve overall survival. We have identified a panel of three antigens that bind to serum autoantibody biomarkers that detect recurrent OVCA nine months in advance of CA125 with an average sensitivity, specificity, and accuracy of 94.7%, 86.7% and 93.3%, respectively. These cloned autoantigens are homologous to paraneoplastic autoantigens, proteins produced by occult tumors that cause neurological or myositis diseases that are autoimmune in origin. Paraneoplastic syndrome patients subsequently develop clinical signs of cancer from these occult tumors. We will further investigate these serum autoantibody biomarkers to 1) our cloned autoantigens and 2) homologous full length paraneoplastic antigenic proteins using sera from a prospective follow-up of women diagnosed with stage III/IV platinum-sensitive serous adenocarcinoma of the ovary. We expect this new cohort to demonstrate the usefulness of this multianalyte test to detect recurrent OVCA prior to CA125. This will be an exploratory study to develop a multi-autoantibody test such as an ELISA-like analysis that can be performed in any clinical serology lab and thus can make an immediate impact in presymptomatic diagnosis of recurrent ovarian cancer. Our expectation is that this test for recurrent OVCA will improve overall survival because it will detect the regrowth of tumors earlier than current methods. Our goal is to identify the most useful and accurate epitopes or paraneoplastic proteins and develop these diagnostic assays so that they can be used for more effective therapeutic interventions in recurrent ovarian cancer.